Hyperbaric oxygen promotes malignant glioma cell growth and inhibits cell apoptosis

Hyperbaric oxygen promotes malignant glioma cell growth and inhibits cell apoptosis
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DOI:
10.3892/ol.2015.3244
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发表时间:
2015-07-01
期刊:
影响因子:
2.9
通讯作者:
Yu, Chun-Jiang
Yu, Chun-Jiang
中科院分区:
医学4区
文献类型:
--
作者:
Wang, Yong-Gang;Zhan, Yi-Ping;Yu, Chun-Jiang

文献摘要

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多形性胶质母细胞瘤(GBM)是成人颅内最常见的恶性肿瘤。临床研究表明,高压氧可以改善胶质瘤患者的预后,减少并发症,但其具体机制尚不清楚。本研究通过建立C57 BL/6 J小鼠颅内移植性胶质瘤模型,探讨高压氧刺激对胶质瘤的直接作用。采用生物发光成像(BLI)技术评估颅内移植GL 261-Luc胶质瘤细胞的体内生长情况,同时采用流式细胞术和免疫组化方法检测并比较反映细胞周期、细胞凋亡和血管生成的生物标志物Ki-67、CD 34和TUNEL的表达。BLI显示高压氧促进脑内移植的GL 261-Luc胶质瘤细胞在体内的生长。流式细胞仪分析显示高压氧促进GL 261-Luc胶质瘤细胞增殖,并阻止细胞周期阻滞。此外,高压氧可抑制移植胶质瘤细胞的凋亡。免疫组织化学分析还表明,高压氧增加了Ki-67和CD 34的阳性染色,而减少了TUNEL染色(细胞凋亡的标志物)。高压氧治疗组微血管密度较对照组明显增加。高压氧治疗促进了移植瘤细胞的生长,并抑制了移植瘤细胞的凋亡。
Glioblastoma multiforme (GBM) is the most frequently diagnosed intracranial malignant tumor in adults. Clinical studies have indicated that hyperbaric oxygen may improve the prognosis and reduce complications in glioma patients; however, the specific mechanism by which this occurs remains unknown. The present study investigated the direct effects of hyperbaric oxygen stimulation on glioma by constructing an intracranial transplanted glioma model in congenic C57BL/6J mice. Bioluminescent imaging (BLI) was used to assess the growth of intracranial transplanted GL261-Luc glioma cells in vivo, while flow cytometric and immunohistochemical assays were used to detect and compare the expression of the biomarkers, Ki-67, CD34 and TUNEL, reflecting the cell cycle, apoptosis and angiogenesis. BLI demonstrated that hyperbaric oxygen promoted the growth of intracranially transplanted GL261-Luc glioma cells in vivo. Flow cytometric analysis indicated that hyperbaric oxygen promoted GL261-Luc glioma cell proliferation and also prevented cell cycle arrest. In addition, hyperbaric oxygen inhibited the apoptosis of the transplanted glioma cells. Immunohistochemical analysis also indicated that hyperbaric oxygen increased positive staining for Ki-67 and CD34, while reducing staining for TUNEL (a marker of apoptosis). The microvessel density was significantly increased in the hyperbaric oxygen treatment group compared with the control group. In conclusion, hyperbaric oxygen treatment promoted the growth of transplanted malignant glioma cells in vivo and also inhibited the apoptosis of these cells.